Bullous pemphigoid (BP) is a severe, autoimmune blistering disease characterized in part by the presence of antibodies in the skin and in the circulation specific for a basement membrane zone (BMZ) protein, the BP antigen. The regions on the antigen important in the pathogenesis of disease and the factors which control the origin of these autoantibodies are unknown. The BP antigen has been recently partially cloned and sequenced. Sera from 25% of patients with BP bind to 2 synthetic peptides encoded by the BP cDNA sequence. This project will characterize the sequences on the BP antigen recognized by B and T cells in these patients. The specific hypotheses to be addressed are: 1) circulating and tissue bound anti-BMZ antibodies in patients with BP recognize specific identical epitopes on the BP antigen; 2) T cells in patients with BP react with specific T cell epitopes on the BP antigen; 3) reactivity of B cells and T cells to specific epitopes correlates with the clinical activity and course of BP; and 4) Class II antigens restrict B and T cell responses in these patients. Antibody binding and T cell responses in patients and controls will be assayed using synthetic peptides and fusion proteins by ELISA technique and in vitro T cell proliferation assays.